Association between different MAP levels and 30-day mortality in sepsis patients: a propensity-score-matched, retrospective cohort study.

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by the infection-related host response disorder. Adequate mean arterial pressure is an important prerequisite of tissue and organ perfusion, which runs through the treatment of sepsis patients, and an appropriate mean arterial pressure titration in the early-stage correlates to the positive outcome of the treatment. Therefore, in the present study, we aimed to elucidate the relationship between early mean arterial pressure levels and short-term mortality in sepsis patients. METHODS: We included all suspected sepsis patients from MIMIC-III database with average mean arterial pressure ≥ 60 mmHg on the first day of intensive care unit stay. Those patients were then divided into a permissive low-mean arterial pressure group (60-65 mmHg) and a high-mean arterial pressure group (> 65 mmHg). Multivariate Cox regression analysis was conducted to analyze the relationship between MAP level and 30-day, 60-day, and 100-day mortality of suspected sepsis patients in the two groups. Propensity score matching, inverse probability of treatment weighing, standardized mortality ratio weighting, PA weighting, overlap weighting, and doubly robust analysis were used to verify our results. RESULTS: A total of 14,031 suspected sepsis patients were eligible for inclusion in our study, among which 1305 (9.3%) had an average first-day mean arterial pressure of 60-65 mmHg, and the remaining 12,726 patients had an average first-day mean arterial pressure of more than 65 mmHg. The risk of 30-day mortality was reduced in the high mean arterial pressure group compared with the permissive low-mean arterial pressure group (HR 0.67 (95% CI 0.60-0.75; p < 0.001)). The higher mean arterial pressure was also associated with lower 60-day and 100-day in-hospital mortality as well as with shorter duration of intensive care unit stay. Patients in the high-mean arterial pressure group also had more urine output on the first and second days of intensive care unit admission. CONCLUSIONS: After risk adjustment, the initial mean arterial pressure of above 65 mmHg was associated with reduced short-term mortality, shorter intensive care unit stay, and higher urine volume in the first two days among patients with sepsis.

Combined exposure to fine particulate matter and high glucose aggravates endothelial damage by increasing inflammation and mitophagy: the involvement of vitamin D.

BACKGROUND: Cardiovascular diseases (CVDs) are related to particulate matter (PM2.5) exposure. Researchers have not clearly determined whether hyperglycemia, a hallmark of diabetes, exacerbates PM2.5-induced endothelial damage. Thus, this study aimed to investigate the combined effects of PM2.5 and high glucose on endothelial damage. RESULTS: Here, we treated human umbilical vein endothelial cells (HUVECs) with 30 mM high glucose and 50 µg/mL PM (HG + PM) to simulate endothelial cells exposed to hyperglycemia and air pollution. First, we showed that HUVECs exposed to PM under high glucose conditions exhibited significant increases in cell damage and apoptosis compared with HUVECs exposed to PM or HG alone. In addition, PM significantly increased the production of reactive oxygen species (ROS) in HUVECs and mitochondria treated with HG and decreased the expression of superoxide dismutase 1 (SOD1), a free radical scavenging enzyme. The coexposure group exhibited significantly increased ROS production in cells and mitochondria, a lower mitochondrial membrane potential, and increased levels of the autophagy-related proteins p62, microtubule-associated protein 1 light chain 3ß (LC3B), and mitophagy-related protein BCL2 interacting protein 3 (Bnip3). Moreover, autophagosome-like structures were observed in the HG + PM group using transmission electron microscopy. The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were also increased through the JNK/p38 signaling pathway in the HG + PM group. As a ROS scavenger, vitamin D treatment effectively protected cells under HG and PM conditions by increasing cell viability, reducing mitochondrial ROS production, and suppressing the formation of mitophagy and inflammation. Furthermore, diabetes was induced in mice by administering streptozotocin (STZ). Mice were treated with PM by intratracheal injection. Vitamin D effectively alleviated oxidative stress, mitophagy, and inflammation in the aortas of mice treated with STZ and PM. CONCLUSION: Taken together, simultaneous exposure to PM and high glucose exerts significant harmful effects on endothelial cells by inducing ROS production, mitophagy, and inflammation, while vitamin D reverses these effects.

Use of Circulating Tumor DNA for the Clinical Management of Metastatic Castration-Resistant Prostate Cancer: A Multicenter, Real-World Study.

BACKGROUND: This study aimed to describe the aberrations of DNA damage repair genes and other important driving genes in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC) using circulating tumor (ctDNA) sequencing and to evaluate the associations between the clinical outcomes of multiple therapies and key genomic alterations in mCRPC, especially DNA damage repair genes. PATIENTS AND METHODS: A total of 292 Chinese patients with mCRPC enrolled from 8 centers. Multigene targeted sequencing was performed on 306 ctDNA samples and 23 matched tumor biopsies. The frequency of genomic alterations were compared with the Stand Up to Cancer-Prostate Cancer Foundation (SU2C-PCF) cohort. The Kaplan-Meier method was used to evaluate progression-free survival (PFS) following standard systemic treatments for mCRPC. Cox regression analyses were performed to determine prognostic factors associated with PFS resulting from treatments for mCRPC. RESULTS: In total, 33 of 36 (91.7%) mutations were found consistently between ctDNA and paired biopsy samples. The most common recurrent genomic alterations were found in AR (34.6%), TP53 (19.5%), CDK12 (15.4%), BRCA2 (13%), and RB1 (5.8%). The frequency of CDK12 alterations (15.4%) in our cohort was significantly higher than that in Western populations (5%-7%). AR amplification and TP53 and/or RB1 alterations were associated with resistance to abiraterone or docetaxel. Patients with a CDK12 defect showed rapid disease progression after abiraterone treatment. However, the clinical outcome after docetaxel treatment was similar between patients with and without CDK12 defects. In multivariate Cox regression analysis, a CDK12 defect was significantly associated with inferior PFS after abiraterone treatment. Patients with a BRCA2 defect showed marked response to both PARP inhibitors and platinum-based chemotherapy. CONCLUSIONS: Our study explored the genomic landscape of Chinese patients with mCRPC at different treatment stages using minimally invasive methods and evaluated the clinical implications of the driver genomic alterations on patients' response to the most widely used therapies for mCRPC. We observed a significantly higher alteration frequency of CDK12 in our cohort compared with the SU2C-PCF cohort.

Modeling the relationship between nursing competence and professional socialization of novice nursing students using a latent growth curve analysis.

Professional skill development and socialization require appropriate guidance and learning. We aimed to examine the effect of self-appraisal of the clinical simulation care task (CSCT-SA) action program on the self-learning effectiveness, self-reflection and insight, caring behavior, nursing competence, and professional socialization of novice nursing students. This study has a single-group longitudinal research design. Five measurement variables, including students' self-learning effectiveness, self-reflection and insight, caring behavior, nursing competence, and professional socialization, were assessed at the baseline, middle, and termination points of the study. The generalized estimating equation and a latent growth curve model were used to examine research hypotheses. A total of 92 students (22 male and 70 female students) completed three point surveys. Students' learning effectiveness, self-reflection and insight, caring behavior, nursing competence, and professional socialization presented a positive growth trajectory throughout the CSCT-SA action program series. In addition, latent growth curve analyses indicated that the levels of nursing competence and professional socialization, as well as the changes in these variables, were positively associated with each other. Findings support the key role played by nursing competence in enhancing students' professional socialization, which suggests that such competence should be improved to promote professional socialization.

Cervical cancer treated with reduced-volume intensity-modulated radiation therapy base on Sedlis criteria (NCCN VS RTOG).

OBJECTIVE: This study aimed to evaluate the clinical efficacy of different target volumes in pelvic radiotherapy in postoperative treatment of cervical cancer based on the Sedlis criteria. METHODS: Patients who admitted to our department for post-operative radiotherapy of cervical cancer from December 2001 to December 2011 and met the Sedlis criteria were retrospectively analysed. The incidences of acute and late radiation injuries, and overall, disease-free and tumour-specific survival with reduced-volume pelvic and whole-pelvis radiotherapy were evaluated and compared. RESULTS: A total of 371 patients were included in the study, including 239 receiving whole-pelvis radiotherapy and 132 receiving reduced-volume pelvic radiotherapy. The volume of contours for mean PTV volumes, bilateral femoral heads and small intestine volumes in reduced-volume pelvic radiotherapy were lower than whole-pelvis radiotherapy; the results were similar to the V10, V20, V30, V40 and V45 for pelvic bone marrow and small intestine dose volume (both p < 0.05). The acute radiation injury observed in the two groups was mainly haematologic toxicity and upper and lower gastrointestinal symptoms. The incidences of acute radiation injury, and late radiation injury of gastrointestinal and urinary tracts were both significantly lower with reduced-volume pelvic radiotherapy than with whole-pelvis radiotherapy (both p < 0.05). Moreover, there was no significant difference in the incidence of lower extremity oedema, or 2-year or 5-year overall, disease-free or tumour-specific survival between groups (all p > 0.05). CONCLUSION: Reduced-volume pelvic radiotherapy could relieve acute and late radiation injuries, especially myelosuppression, and did not affect long-term survival. Advanced in knowledge: Our study shows that reduced-volume base on National Comprehensive Cancer Network 2016 is more fit for cervical cancer than others.

Prostate cancer treated with reduced-volume intensity-modulated radiation therapy: Report on the 5-year outcome of a prospective series.

How to define a clinical target volume (CTV) as small as possible for prostate cancer to reduce the dose received by normal organs is an interesting study. We conduct a research to analyze the clinical efficacy of intensity modulated radiotherapy (IMRT) using reduced CTV in the treatment of prostate cancer. From January 2006 to June 2010, 78 patients with prostate cancer were treated with IMRT according to this institutional protocol. Of them, 18 had stage II tumors, 39 had stage III tumors, and 21 had stage IVa tumors. Clinical outcomes included overall survival, biochemical recurrence, recurrence-free survival, and acute and chronic injuries caused by radiotherapy. Risk factors were evaluated using the Cox regression model. As of December 31, 2014, all patients completed radiotherapy as planned. Myelosuppression was mostly grade 1, acute urinary injury was mostly grades 1 and 2, and intestinal injury was mostly grade 1. The 5-year follow-up rate was 91.0%. The overall, progression-free, biochemical recurrence-free, and distant metastasis-free survival rates were 82.1%, 79.4%, 84.6%, and 94.9%, respectively. Tumor volumes defined by small target volumes and Radiation Therapy Oncology Group were 274.21 ±â€Š92.64 and 600.68 ±â€Š113.72, respectively, representing a significant difference (P < .05). Age, prostate-specific antigen level, eastern cooperative oncology Group score, Gleason score, and volume of CTV were independent risk factors for mortality and disease progression. Our findings indicated that IMRT with reduced CTV have less acute and chronic injuries caused by radiation, particularly grade 3 or higher urinary and intestinal injuries, while ensuring survival benefits and protecting the hematopoietic function.

Long-term cancer-related fatigue outcomes in patients with locally advanced prostate cancer after intensity-modulated radiotherapy combined with hormonal therapy.

The aim of our study was to investigate the relationship between cancer-related fatigue and clinical parameters, and the effect factors of fatigue for the prostate cancer patients. Long-term follow-up is performed using the Fatigue Symptom Inventory before treatment (A), at the end of intensity-modulated radiotherapy (B), and 3 months (C), 12 months (D), 24 months (E), 36 months (F), and 48 months (G) after the end of intensity-modulated radiotherapy. Three dimensions of fatigue are assessed during follow-up: severity, perceived interference with quality of life, and duration in the past week. In all, 97 patients with locally advanced prostate cancer were enrolled in the study. Median follow-up time was 43.9 months. The fatigue index was significantly higher in the prostate-specific antigen >20 ng/mL, Gleason score >8, the Eastern Cooperative Oncology Group scores, and the higher education. The most severe fatigue occurred at time points B and C. The score for duration of fatigue fluctuated across the time points, with significantly increased scores at time points D, E, and F.In conclusion, we show that cancer-related fatigue is the important symptom which affects the quality of life for the prostate cancer patients. For patients with locally advanced prostate cancer with a high Eastern Cooperative Oncology Group score, a Gleason score of >8 points, prostate-specific antigen levels of >20 ng/mL, and high education, attention should be paid to the interference of fatigue with quality of life, especially general level of activity, ability to concentrate, and mood, after radiotherapy combined with hormonal therapy.

C-Reactive Protein is a Prognostic Marker for Patients with Castration-Resistant Prostate Cancer.

INTRODUCTION: As an acute-phase protein synthesized in response to systemic inflammation, the C-reactive protein (CRP) has been shown to be an independent prognostic factor for patients with castration-resistant prostate cancer (CRPC). The aim of this study was to investigate the association between CRP and progression-free survival (PFS), overall survival (OS) and radiological response in CRPC patients treated with docetaxel. METHODS: 115 histologically confirmed CRPC patients who were treated with docetaxel chemotherapy from 2008 to 2013 were selected. Univariable and multivariable Cox regression models were used to predict the association of CRP as a dichotomous variable with PFS and OS after chemotherapy initiation. RESULTS: None of the clinicopathological features were associated with the CRP. In Kaplan-Meier analysis, the median PFS (9.8 vs. 7.5 months, p < 0.001) and OS (26.5 vs. 13.5 months, p = 0.002) were higher in patients who did not have an elevated CRP than in those with an elevated CRP. In univariable analysis, the pretreatment CRP was significantly associated with PFS (p < 0.001) and OS (p = 0.003).In multivariable analysis, patients with a CRP > 8 mg/l were at significantly higher risk of tumor progress (hazard ratio (HR) 2.184; 95% confidence interval (CI) 1.401-3.403; p = 0.001) and death (HR 2.003; 95% CI 1.285-3.121; p = 0.002) than patients with a CRP ≤ 8 mg/l. CONCLUSIONS: CRP may be an important biomarker of PFS and OS in CRPC patients treated with docetaxel. The findings require validation in further prospective, large cohort-size studies.

Hypoxia-inducible factor-1α protects cervical carcinoma cells from apoptosis induced by radiation via modulation of vascular endothelial growth factor and p53 under hypoxia.

BACKGROUND: The aim of the study was to assess the role of irradiation in the expression of HIF-1a, VEGF, and P53 in human cervical carcinoma cells under a simulated hypoxia environment. MATERIAL/METHODS: The tetrazolium-based colorimetric cellular assay (MTT) and flow cytometry (FCM) were used to detect the growth inhibition rates of HeLa cells in different groups. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to observe gene and protein expression of HIF-1α, VEGF, and P53. The effect of HIF-1α on radioresistance and expression of VEGF and P53 were confirmed with the HIF-1α siRNA in vivo and in vitro. RESULTS: Hypoxic conditions enhanced the radiation resistance dependent on HIF-1α by elevating the expression of VEGF and inhibiting the expression of p53. After transfection of HIF-1α siRNA, MTT assay showed the survival rates were increased in the cells receiving irradiation under hypoxia. The expression of VEGF decreased significantly more than that of cells transfected with sense oligodeoxynucleotides, while an opposite result was found in the expression of P53 protein in the same X-ray dose (p<0.05). In vivo, the radioresistance of HIF-1α was consistent with the results in vitro. CONCLUSIONS: In the future, we might inhibit human cervical cancer progression and enhance the radiosensitivity by inhibiting HIF-1α to reduce VEGF and increase P53 expression. The challenge is how to use this information to optimize cancer therapy.

Inhibition of TRPM7 channels reduces degranulation and release of cytokines in rat bone marrow-derived mast cells.

BACKGROUND: mast cells play an important role in airway inflammation in asthma. The transient receptor potential melastatin-like 7 (TRPM7) channel is expressed in primary human lung mast cells and plays a critical role for cell survival. This study aimed to investigate the role of TRPM7 on degranulation and release of cytokines in rat bone marrow-derived mast cells (BMMCs). METHODS: the expression levels of TRPM7 were observed by immunocytochemistry and RT-PCR between normal and asthmatic rat BMMCs. TRPM7-specific shRNA and 2-aminoethoxydiphenyl borate (2-APB) and specific shTRPM7 were used to inhibit the function of TRPM7. Degranulation levels were analyzed by beta-hexosaminidase assay. Histamine, TNF-α, IL-6 and IL-13 levels were measured by ELISA. RESULTS: the expression of TRPM7 was significantly higher in asthmatic rat BMMCs than in the normal control group. After application of 2-APB and down-regulation of TRPM7, the beta-hexosaminidase activity and secretion of histamine, IL-6, IL-13 and TNF-α were significantly decreased in the asthmatic group compared to the control group. CONCLUSION: this study indicates that TRPM7 channels may be involved in the process of degranulation and release of cytokines in rat bone marrow-derived mast cells.

Long-term quality of life outcomes in patients with locally advanced prostate cancer after intensity-modulated radiotherapy combined with androgen deprivation.

With great improvements in survival in patients with locally advanced prostate cancer, quality of life (QOL) is becoming an important factor in the selection of treatment. The aim of this study was to evaluate changes in health-related QOL in patients with locally advanced prostate cancer after intensity-modulated radiotherapy (IMRT) combined with androgen deprivation therapy. Patients were treated with IMRT combined with androgen deprivation. Total dose to the prostate was 68.2 Gy (2.2 Gy per fraction), and patients received 50 mg of oral Casodex once daily and 3.6 mg of subcutaneous Zoladex once every 28 days for 2.5 years. QOL was measured using the Expanded Prostate Cancer Index Composite. The time points were baseline, end of radiotherapy, and 3, 12, 36, 48, and 60 months after radiotherapy. From 2002 to 2007, a total of 87 patients were enrolled. Median follow-up time was 76.8 months. Compared with baseline, all four domain summary scores were decreased to varying degrees. Statistically significant changes in the urinary, bowel, and hormonal domain scores were observed (P < 0.05). The changes in scores for urinary incontinence and dysuria were -13.0 ± 8.3 and -6.12 ± 3.9, respectively (P < 0.05). QOL was decreased in patients with locally advanced prostate cancer after IMRT combined with androgen deprivation therapy in all four primary domains, especially in urinary, bowel, and hormonal domains. Nevertheless, the treatment was well tolerated in most patients during the 5 years of follow-up.

Intensity-modulated radiotherapy combined with endocrine therapy for intermediate and advanced prostate cancer: long-term outcome of Chinese patients.

AIM: The aim of this study was to evaluate acute adverse events and efficacy of three-dimensional intensity- modulated radiotherapy (IMRT) combined with endocrine therapy for intermediate and advanced prostate cancer. METHODS: Sixty-seven patients were treated with three-dimensional IMRT combined with maximum androgen blockade. The correlation between radiation-induced rectal injury and clinical factors was further analyzed. RESULTS: After treatment, 21 patients had complete remission (CR), 37 had partial remission (PR), and nine had stable disease (SD), with an overall response rate of 86.5%. The follow-up period ranged from 12.5 to 99.6 months. Thirty-nine patients had a follow-up time of ≥ five years. In this group, three-year and five-year overall survival rates were 89% and 89.5%, respectively; three-year and five-year progression-free survival rates were 72% and 63%. In univariate analyses, gross tumor volume was found to be prognostic for survival (χ2 = 5.70, P = 0.037). Rates of leucopenia and anemia were 91.1% and 89.5%, respectively. Two patients developed acute liver injury, and a majority of patients developed acute radiation proctitis and cystitis, mainly grade 1/2. Tumor volume before treatment was the only prognostic factor influencing the severity of acute radiation proctitis (P < 0.05). CONCLUSIONS: IMRT combined with endocrine therapy demonstrated promising efficacy and was well tolerated in patients with intermediate and advanced prostate cancer.

Mitochondrial DNA 4977 bp deletion is a common phenomenon in hair and increases with age.

Mitochondrial DNA (mtDNA) is believed to be particularly susceptible to oxidative damage during aging, resulting in mtDNA point mutations, duplications, and deletions. Although mtDNA deletions have been reported in various human tissues, e.g., the brain, heart, and skeletal muscle, little is known about the occurrence in hair. Therefore, we screened for the presence of mtDNA 13162 bp, 10422 bp, 7663 bp, 7436 bp, 4989 bp, and 4977 bp deletions in 90 hair samples from subjects aged 5 days to 91 years by using polymerase chain reaction (PCR) and investigated the deletion load by TaqMan probe-based real-time PCR. We detected the mtDNA 4977 bp deletion in hair samples, but none of the other deletions that were screened for. The proportion of mtDNA 4977 deletion carriers was 98.3% (89/90) and the deletion loads increased from 0 to 1.436 ± 0.2086% of the total mtDNA with an exponential increase with age (r = 0.677, p < 0.05). These results suggest that mtDNA 4977 bp deletion is a common phenomenon in hair and increases with age. These findings expand our understanding of the tissue-specific distribution of mtDNA deletions.

A preliminary study on the consistency between the non-surgical staging and the surgical-pathological staging in oesophageal carcinoma.

OBJECTIVES To evaluate the consistency between the clinical staging of non-surgically treated oesophageal carcinoma (preliminary draft) and the surgical-pathological staging of the oesophageal carcinoma. METHODS Comprehensive clinical data from 112 patients with oesophageal cancer were collected from January 2009 to June 2010. Based on the clinical staging standard for oesophageal carcinomas treated with non-surgical methods, the preoperative TNM staging was performed and the results were compared with pTNM. The Kappa statistic was used to analyse the degree of consistency. RESULTS The Kappa values from the T staging, N staging and TNM staging of surgical-pathological results were 0.545, 0.615 and -0.090, respectively. CONCLUSIONS Consistency was observed between the non-surgical T staging and N staging and the postoperative pathological T staging and N staging, but the degree of consistency was only moderate. Additionally, no consistency was observed between the TNM staging results from the two staging systems. Whether the non-surgical staging system can replace the pathological staging system and its significance in evaluating the prognosis remain to be determined.

[Effect of ionization on the expression of hypoxia-inducible factor-1alpha and VEGF in hepatocellular carcinoma HepG2 cells under anoxic condition].

OBJECTIVE: To investigate the effect of ionization on the expression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor (VEGF) in human hepatocellular carcinoma HepG2 cells under anoxic condition, and search for an effective method for improving the radiosensitivity of the tumor cells. METHODS: HepG2 cells were divided into 4 groups, namely the control group, hypoxia group, ionization radiation group, and hypoxia and radiation group, with corresponding treatments. The cell apoptosis was detected by fluorescence microscope, and the cell viability analyzed by MTT assay. The expressions of HIF-1alpha and VEGF mRNAs were detected by RT-PCR. RESULTS: A few apoptotic cells were found in hypoxia group, but significant apoptosis occurred in the radiation group; fewer apoptotic cells were observed in the hypoxia and radiation group than in the hypoxia group. The viable cell fraction increased in the order of the control group>hypoxia group> hypoxia plus radiation group> radiation group (P<0.05), and the expression of HIF-1alpha mRNA increased in the order of hypoxia plus radiation group>hypoxia group>radiation group (P<0.05), and no significant difference was found in the radiation group and control group. The expression of VEGF mRNA increased in the order of hypoxia plus radiation group> hypoxia group>radiation group>control group (P<0.05). CONCLUSION: The expression of HIF-1alpha may protect the hepatocellular carcinoma cells from damages by radiation in hypoxic condition, and HIF-1alpha decreases the radiosensitivity of the cells possibly by inducing VEGF expression.